德国马克斯普朗克代谢研究所Jens C. Brüning小组报道，下丘脑PNOC/NPY神经元是瘦素控制的能量稳态的介质。相关论文发表在2025年4月23日出版的《细胞》杂志上。
课题组研究人员发现瘦素通过PNOC神经元调节食欲和体重，而在下丘脑弓状核表达PNOC的神经元中，瘦素受体（Lepr）表达的缺失与嗜食和肥胖有关。在没有麻风基因的肥胖背景下，恢复PNOC神经元中麻风基因的表达可显著减轻体重。PNOC神经元的麻风失活增加了下丘脑PNOC神经元中不表达刺痛肽相关肽（Agrp）的神经肽Y （Npy）的表达。PNOC/NPY神经元的选择性化学激活促进摄食的程度与激活所有PNOCARC神经元的程度相同，PNOCARC神经元中Npy的过表达促进了贪食和肥胖。因此，研究团队将PNOC/NPYARC神经元作为瘦素作用的另一个关键介质，并作为肥胖治疗的一个有希望的靶点。
据了解，瘦素在大脑中起抑制食欲的作用，然而，瘦素的厌食作用背后的神经回路尚未完全确定。表达前pronoceptin （PNOC）的神经元介导小鼠饮食诱导的贪食和体重增加。
附：英文原文
Title: Hypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis
Author: Marie H. Solheim, Sima Stroganov, Weiyi Chen, P. Sicilia Subagia, Corinna A. Bauder, Daria Wnuk-Lipinski, Almudena Del Río-Martín, Tamara Sotelo-Hitschfeld, Cait A. Beddows, Paul Klemm, Garron T. Dodd, Sofia Lundh, Anna Secher, F. Thomas Wunderlich, Lukas Steuernagel, Jens C. Brüning
Issue&Volume: 2025-04-23
Abstract: Leptin acts in the brain to suppress appetite, yet the responsible neurocircuitries underlying leptin’s anorectic effect are incompletely defined. Prepronociceptin (PNOC)-expressing neurons mediate diet-induced hyperphagia and weight gain in mice. Here, we show that leptin regulates appetite and body weight via PNOC neurons, and that loss of leptin receptor (Lepr) expression in PNOC-expressing neurons in the arcuate nucleus of the hypothalamus (ARC) causes hyperphagia and obesity. Restoring Lepr expression in PNOC neurons on a Lepr-null obese background substantially reduces body weight. Lepr inactivation in PNOC neurons increases neuropeptide Y (Npy) expression in a subset of hypothalamic PNOC neurons that do not express agouti-related peptide (Agrp). Selective chemogenetic activation of PNOC/NPY neurons promotes feeding to the same extent as activating all PNOCARC neurons, and overexpression of Npy in PNOCARC neurons promotes hyperphagia and obesity. Thus, we introduce PNOC/NPYARC neurons as an additional critical mediator of leptin action and as a promising target for obesity therapeutics.
DOI: 10.1016/j.cell.2025.04.001
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00403-9